This Integrated Pre-Clinical/Clinical Program from City of Hope National Medical Center (COH) proposes to develop and improve methods for genetic treatment of HIV-1 using antiviral RNA. There are three basic science projects aimed at improved gene transfer, gene expression, and HIV inhibition using retroviral and lentiviral vectors. Project 1 at Children's Hospital Los Angeles will evaluate the expression of improved vectors in monocytes and T-cells after transduction of human hematopoietic stem cells. Project 2 at the Beckman Research Institute of COH (BRICOH) will study improved stability of expression of antiviral RNA target4ed to HIV. Project 3 at BRICOH is devoted to comparative studies of improved retroviral and lentiviral vectors. In Project 4, the Clinical Trials Center will complete two comparative trials of experimental autologous stem-cell transplantation (SCT) of CD34+ peripheral blood progenitor cells (PBPC) transduced with a retrovirus encoding a double hammerhead ribozyme targeted to TAT and REV. one study, in AIDS patients with non-Hodgkin's lymphoma, utilizes an ablative marrow conditioning regimen, and the other, in healthy HIV-1 infected persons, will use hydroxyurea for partial cytoreduction of marrow. The basic science and laboratory programs are supported by three core areas. The Administrative Center, will oversee the management of the basic science and clinical studies. The DNA/RNA Analytical Lab will evaluate marrow and blood specimens post transplantation for the presence and stability of expression of the ribozyme transgene. The Virology Lab, will provide support for HIV analyses and assessment of antiviral effects of new anti-HIV RNAs.